Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City IA, USA.
Front Cell Infect Microbiol. 2012 Feb 21;2:18. doi: 10.3389/fcimb.2012.00018. eCollection 2012.
Staphylococcus aureus is a major cause of infective endocarditis (IE) and sepsis. Both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains cause these illnesses. Common S. aureus strains include pulsed-field gel electrophoresis (PFGE) types USA200, 300, and 400 types where we hypothesize that secreted virulence factors contribute to both IE and sepsis. Rabbit cardiac physiology is considered similar to humans, and rabbits exhibit susceptibility to S. aureus superantigens (SAgs) and cytolysins. As such, rabbits are an excellent model for studying IE and sepsis, which over the course of four days develop IE vegetations and/or fatal septicemia. We examined the ability of MRSA and MSSA strains (4 USA200, 2 USA300, 2 USA400, and three additional common strains, FRI1169, Newman, and COL) to cause vegetations and lethal sepsis in rabbits. USA200, TSST-1(+) strains that produce only low amounts of α-toxin, exhibited modest LD(50) in sepsis (1 × 10(8) - 5 × 10(8)) colony-forming units (CFUs), and 3/4 caused significant IE. USA200 strain MNPE, which produces high-levels of α-toxin, was both highly lethal (LD(50) 5 × 10(6) CFUs) and effective in causing IE. In contrast, USA300 strains were highly effective in causing lethal sepsis (LD(50)s 1 × 10(6) and 5 × 10(7) CFUs) but were minimally capable of causing IE. Strain Newman, which is phylogenetically related to USA300 strains, was not highly lethal (LD(50) of 2 × 10(9) CFUs) and was effective in causing IE. USA400 strains were both highly lethal (LD(50)s of 1 × 10(7) and 5 × 10(7) CFUs) and highly effective causes of IE. The menstrual TSS isolate FRI1169, that is TSST-1(+), produces high-levels of α-toxin, but is not USA200, was both highly lethal and effective in causing IE. Additional studies showed that phenol soluble modulins (PSMs) produced by FRI1169 were important for sepsis but did not contribute to IE. Our studies show that these clonal groups of S. aureus differ in abilities to cause IE and lethal sepsis and suggest that secreted virulence factors, including SAgs and cytolysins, account for some of these differences.
金黄色葡萄球菌是感染性心内膜炎（IE）和败血症的主要原因。耐甲氧西林金黄色葡萄球菌（MRSA）和甲氧西林敏感金黄色葡萄球菌（MSSA）菌株均可引起这些疾病。常见的金黄色葡萄球菌菌株包括脉冲场凝胶电泳（PFGE）类型 USA200、300 和 400 型，我们假设分泌的毒力因子有助于 IE 和败血症的发生。兔心脏生理学被认为与人类相似，且兔子易受金黄色葡萄球菌超抗原（SAg）和细胞毒素的影响。因此，兔子是研究 IE 和败血症的理想模型，在这一过程中，兔子在四天内形成 IE 赘生物和/或致命败血症。我们检测了 MRSA 和 MSSA 菌株（4 株 USA200、2 株 USA300、2 株 USA400 和另外 3 株常见菌株 FRI1169、Newman 和 COL）引起兔子 IE 赘生物和致死性败血症的能力。仅产生少量 α-毒素的 USA200 TSST-1(+) 菌株在败血症中表现出中等 LD(50)（1×10(8) - 5×10(8)）菌落形成单位（CFU），其中 3/4 株可引起明显的 IE。产生高水平 α-毒素的 USA200 菌株 MNPE 既具有高度致死性（LD(50) 5×10(6) CFU），又能有效引起 IE。相比之下，USA300 菌株在引起致命性败血症方面非常有效（LD(50) 1×10(6) 和 5×10(7) CFU），但引起 IE 的能力却很有限。与 USA300 菌株具有亲缘关系的菌株 Newman ，其致死性不高（LD(50) 2×10(9) CFU），但能有效引起 IE。USA400 菌株在引起致死性败血症方面均具有高度致死性（LD(50) 1×10(7) 和 5×10(7) CFU）和高效性，可引起 IE。月经性 TSS 分离株 FRI1169 为 TSST-1(+)，产生高水平的 α-毒素，但它不是 USA200 株，对 IE 既具有高度致死性，又具有高效性。进一步的研究表明，FRI1169 产生的酚可溶性调节素（PSMs）对败血症很重要，但对 IE 没有贡献。我们的研究表明，这些金黄色葡萄球菌克隆群在引起 IE 和致命性败血症的能力上存在差异，并且表明分泌的毒力因子，包括 SAg 和细胞毒素，在一定程度上解释了这些差异。
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